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Background: Despite significant survival improvement in human epidermal growth factor receptor 2 (HER2) blockade for HER2-positive breast cancer, resistance to anti-HER2 remains inevitable. Subsequent anti-HER2 with continuing trastuzumab beyond progression is acceptable with limited efficacy when other anti-HER2 treatment is unavailable. This single-arm, phase II study (SYSUCC-005) aimed to explore the efficacy of switching mode for HER2-positive refractory metastatic breast cancer.Methods: Patients with HER2-positive metastatic breast cancer rapidly progressing during pre-trastuzumab from six hospitals in China were designed to switch to lapatinib 1,250 mg orally once per day continuously plus capecitabine (1,000 mg/m2 orally twice per day on days 1-14) or vinorelbine (25 mg/m2 intravenously once per day on days 1 and 8) of each 21-day cycle. The primary endpoint was progression-free survival (PFS).Results: Between January 5, 2015 and May 31, 2020, 159 patients were eligible in this study. The median follow-up was 33.1 months, a median PFS of 8.5 months was achieved. Brain metastases (hazard ratio [HR] = 1.582, 95% confidence interval [CI] 1.019- 2.453, P = 0.041) and ≥ 2 metastatic sites (HR = 1.679, 95% CI 1.151-2.450, P = 0.007) were independent prognostic factors for PFS. The most common grade ≥ 3 adverse events were diarrhea (3.8%) and hand-foot syndrome (9.4%).Conclusion: The switching mode showed predominant efficacy, which might be a prior therapeutic option over continuing mode in subsequent anti-HER2 therapy for patients with HER2-positive refractory metastatic breast cancer.Trial Registration: This trial was registered on ClinicalTrials.gov ( NCT02362958 ) on 13/02/2015. [ABSTRACT FROM AUTHOR]

Lessons Learned: Moxifloxacin plus continuation of the previous treatment of physician's choice shows promising efficacy in patients with metastatic breast cancer.The addition of moxifloxacin shows well‐tolerated toxicities. Background: Recent studies have confirmed bacterial infection as an important contributor in cancer. Elimination of tumor‐associated microbes may lead to a reduction in tumors and improved survival. Moxifloxacin is an orally administrated fourth‐generation quinolone with broad‐spectrum coverage against tumor‐associated bacteria. Methods: In this study, we assessed the efficacy and safety of moxifloxacin in combination with treatment of physician's choice (TPC) in patients with metastatic breast cancer (MBC). In this single‐arm, phase II study, we recruited 30 patients with MBC who had a trend toward disease progression (stable disease [SD] with increased tumor size) during TPC before enrollment at Sun Yat‐sen University Cancer Center between January 1 and July 30, 2018. Eligible patients were given moxifloxacin once daily at a dose of 400 mg from days 1 to 7 of a 28‐day cycle, in addition to continuing to receive the therapy previously selected by their physicians. Tumor response was determined according to RECIST (version 1.1). Progression‐free survival (PFS) was calculated using the Kaplan‐Meier method. Results: The concomitant use of moxifloxacin and previous TPC yielded a median PFS of 6.6 months (95% confidence interval [CI]: 4.0–9.1) and a 1‐year PFS of 25.9% (95% CI: 10.0%–41.9%). Objective responses were achieved in seven (23.3%, 95% CI: 7.3%–39.4%) patients. The clinical benefit rate was 46.7% (95% CI: 27.7%–65.6%). No grade 4 adverse events (AEs) and four grade 3 AEs were observed, none of which were considered to have definite relation to moxifloxacin. Conclusion: The combination of moxifloxacin with previous TPC shows promising efficacy and well‐tolerated toxicities in patients with MBC. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node-negative, triple-negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes.Methods: The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat-Sen University Cancer Center. For the meta-analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population.Results: Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence-free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/bN0M0) were included in the meta-analysis. The meta-analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease.Conclusions: Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta-analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy. [ABSTRACT FROM AUTHOR]

The role of adjuvant ovarian suppression or ablation (OS/OA) in premenopausal women with hormone receptor-positive breast cancer remains controversial. The purpose of our study was to examine which patients might benefit from the addition of OS/OA to tamoxifen. We analyzed the data of 2065 premenopausal patients with hormone receptor-positive invasive ductal carcinomas who were treated at Sun Yat-Sen University Cancer Center from 2000 to 2008. The five-year disease-free survival rate (DFSR) and overall survival rate (OSR) were compared by menstrual status and treatment. Compared with patients older than forty years of age, patients younger than forty years old had significant lower DFSRs and OSRs. The addition of OS/OA to tamoxifen increased the DFSR and OSR of patients with normal menstrual cycles after chemotherapy, regardless of their age at diagnosis. Patients with normal menstrual cycles after chemotherapy are the main beneficiaries of an adjuvant OS/OA. [ABSTRACT FROM AUTHOR]

Lessons Learned: Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)‐resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor‐positive and AI‐resistant disease in this phase II, single‐arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage. Background: Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR‐positive triple‐negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)‐positive and AR‐positive advanced breast cancer. Methods: A Simon's two‐stage, phase II, single‐arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression‐free survival (PFS), and tolerability. Results: A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow‐up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated. Conclusion: Bicalutamide in combination with another AI did not show synergistic activity in patients with ER‐positive breast cancer and AI resistance. Results suggest that no more large‐sample clinical trials should be conducted in this population for overcoming endocrine resistance. [ABSTRACT FROM AUTHOR]

Background: Topoisomerase II alpha (TOP2A) protein has been shown to be a proliferation marker associated with tumor grade and Ki67 index. The prognostic effect of TOP2A seems different among different subtypes of breast cancer. The current study evaluated the prognostic impact of TOP2A protein on luminal breast cancer.Method: Altogether 434 stage I-II luminal breast cancer patients who underwent curative surgery in Sun Yat-Sen University Cancer Center between 2007 and 2009 were enrolled. TOP2A protein expression was assessed by immunohistochemistry. Clinical and pathological data were retrospectively collected.Result: With a cut-off value of 30%, 127 (29.3%) patients were classified as TOP2A overexpression. TOP2A overexpression was associated with a higher tumor grade and Ki67 index. Patients with TOP2A high expression showed a significantly higher rate of distant metastasis and shorter distant metastasis free survival (DMFS) compared with patients with low TOP2A expression. The prognostic influence of TOP2A expression was more significant in years 5-8 after diagnosis, and more pronounced in stage II patients, luminal B disease, and patients treated with adjuvant endocrine therapy alone. Multivariate survival analysis revealed TOP2A overexpression was an independent fact for worse DMFS.Conclusion: TOP2A protein showed a time dependent influence on prognosis in stage I-II luminal breast cancer, suggesting it might be a potential predictor of late recurrence for this group of patients. [ABSTRACT FROM AUTHOR]

Background: Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer.Methods: We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/m2 intravenously once per day on days 1-5) plus capecitabine (1000 mg/m2 orally twice per day on days 1-14), or capecitabine alone (1250 mg/m2 orally twice per day on days 1-14), until disease progression or unacceptable toxicity occurred. Patients, physicians, and assessors were not masked to treatment allocation; however, an independent radiology review committee used to additionally assess response was masked to allocation. The primary endpoint was centrally assessed (by an independent radiology review committee) progression-free survival, and analysed using the Kaplan-Meier product-limit method in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. Follow-up is ongoing. This study is registered at ClinicalTrials.gov, number NCT02253459.Findings: Between Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81-10·32) for the utidelone plus capecitabine group and 4·55 months (2·55-9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95-9·92) compared with 4·27 months (3·22-5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36-0·59; p<0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 [22%] of 267 patients vs 1 [<1%] of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 [8%] of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 [7%] of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three [1%] patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two [2%] patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related.Interpretation: Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer.Funding: Beijing Biostar Technologies, Beijing, China. [ABSTRACT FROM AUTHOR]